This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Topiramate, a substituted fructo-pyranose derivative, is a promising agent for the treatment of cocaine dependence, presumably because by reducing its rewarding affects associated with abuse liability. We propose an experiment using state-of-the-art human abuse liability assessment techniques to examine the subjective, behavioral, and physiological effects of cocaine both alone and in combination with topiramate. The study will be double-blind and placebo-controlled using a balanced (for sequence and position) cross-over design in male and female non treatment-seeking cocaine abusers (total N = 24). The experiment will test the hypothesis that chronically-administered topiramate will significantly reduces acute cocaine-mediated changes in subjective mood and other abuse liability assessments. As a secondary objective of this experiment, we will characterize cocaine's effects on cognition and physiological response in non-fatigued subjects during drug-taking, and determine if, and by how much, these effects are altered by topiramate. In summary, this experiment provides a proof-of-concept analysis of topiramate's ability to reduce cocaine's abuse potential. The results of this human laboratory study should provide a solid basis for planning clinical trials examining the safety and effectiveness of topiramate for the treatment of cocaine-dependent individuals.